Usage
Armodafinil is prescribed for improving wakefulness in patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnea (OSA), and shift work sleep disorder (SWSD). It belongs to the pharmacological classification of wakefulness-promoting agents or eugeroics, a type of central nervous system stimulant. Armodafinil’s precise mechanism of action is not fully understood, but it’s thought to work by increasing dopamine levels in the brain by inhibiting dopamine reuptake at the dopamine transporter (DAT). It may also influence other neurotransmitters like histamine and orexin, which play a role in regulating the sleep-wake cycle.
Alternate Names
Armodafinil is also known as the R-enantiomer of modafinil. Popular brand names under which it is marketed include Nuvigil.
How It Works
Pharmacodynamics: Armodafinil promotes wakefulness by influencing several neurotransmitter systems in the brain. The primary mechanism is believed to involve the inhibition of dopamine reuptake, leading to increased extracellular dopamine levels. It may also have some effects on other neurotransmitter systems such as histamine and orexin, but these are not as well-established.
Pharmacokinetics:
- Absorption: Armodafinil is readily absorbed after oral administration, reaching peak plasma concentrations in about 2 hours. Food does not significantly affect its absorption.
- Metabolism: It is primarily metabolized in the liver, partially by the cytochrome P450 (CYP) 3A4 enzyme system, and forms the inactive metabolite armodafinil acid.
- Elimination: Armodafinil is primarily eliminated through the kidneys (renal excretion), with a smaller portion eliminated in the feces. The half-life of armodafinil is about 15 hours.
Mode of Action: Armodafinil primarily inhibits the dopamine transporter, increasing the concentration of dopamine in the synaptic cleft. It may also modestly impact histamine and orexin systems, further contributing to its wakefulness-promoting effects.
Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Armodafinil binds to the dopamine transporter, inhibiting dopamine reuptake. Its actions on other neurotransmitter systems are not fully characterized but are likely mediated by indirect modulation.
Dosage
Standard Dosage
Adults:
The standard dose is 150 mg taken orally once a day in the morning for narcolepsy and obstructive sleep apnea. For shift work sleep disorder, 150 mg is taken approximately 1 hour before the start of the work shift. Doses up to 250 mg have been well-tolerated, but there’s no consistent evidence of increased benefit beyond 150 mg/day.
Children:
The safety and efficacy of armodafinil have not been established in children younger than 17 years old. The use and dose must be determined by a doctor, taking into account the child’s weight, age, and specific medical condition.
Special Cases:
- Elderly Patients: A lower initial dose should be considered, and close monitoring is recommended due to age-related changes in drug clearance.
- Patients with Renal Impairment: Dosage adjustments may be necessary for those with renal impairment. The safety and efficacy have not been formally established in patients with severe renal impairment.
- Patients with Hepatic Dysfunction: A reduced dose is recommended in patients with severe hepatic impairment due to decreased drug clearance.
- Patients with Comorbid Conditions: Close monitoring is necessary in patients with pre-existing cardiovascular disease. Patients with a history of psychiatric disorders (e.g., depression, psychosis, mania) should be monitored closely, and treatment should be discontinued if psychiatric symptoms worsen.
Clinical Use Cases
Armodafinil is not typically used in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations. Its primary indication is the treatment of excessive sleepiness related to the specific sleep disorders mentioned earlier.
Dosage Adjustments
Dosage adjustments should be individualized based on the patient’s specific situation, including factors such as renal or hepatic dysfunction, age, and the presence of other medical conditions. Genetic polymorphisms affecting drug metabolism may also necessitate dose adjustments.
Side Effects
Common Side Effects:
Headache, nausea, dizziness, insomnia, dry mouth, anxiety, diarrhea, and rash.
Rare but Serious Side Effects:
Serious skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), angioedema, anaphylaxis, multi-organ hypersensitivity reactions, psychiatric symptoms (depression, anxiety, hallucinations, mania, aggressive behavior), changes in heart rhythm, and chest pain.
Long-Term Effects:
Potential long-term effects of armodafinil are not fully known, but they may include dependence, tolerance, and cardiovascular effects with prolonged use.
Adverse Drug Reactions (ADR):
Any serious skin reaction, signs of angioedema or anaphylaxis, severe psychiatric symptoms, or significant cardiovascular effects should be considered ADRs requiring immediate medical intervention.
Contraindications
- Hypersensitivity to armodafinil or modafinil.
- Patients with a recent history of myocardial infarction or unstable angina.
Drug Interactions
Armodafinil interacts with numerous medications, including:
- CYP3A4 substrates: It can decrease the effectiveness of drugs metabolized by CYP3A4 (e.g., hormonal contraceptives, some antidepressants, some immunosuppressants).
- CYP3A4 inhibitors: These can increase armodafinil levels (e.g., some antifungals, some antibiotics).
- CYP3A4 inducers: These can decrease armodafinil levels (e.g., some anticonvulsants).
- MAOIs: Concurrent use can increase the risk of serotonin syndrome.
- Stimulants: Concurrent use can lead to additive stimulant effects.
Alcohol should be avoided while taking armodafinil.
Pregnancy and Breastfeeding
Armodafinil’s safety during pregnancy hasn’t been established. There have been reports of intrauterine growth restriction and spontaneous abortion. The effectiveness of hormonal contraceptives can be reduced for up to one month after discontinuation of armodafinil. There are limited data regarding breastfeeding, but a small amount of armodafinil can pass into breast milk. A pregnancy registry is available for collecting information on armodafinil exposure during pregnancy.
Drug Profile Summary
- Mechanism of Action: Inhibits dopamine reuptake, increases dopamine levels.
- Side Effects: Headache, nausea, dizziness, insomnia, serious skin reactions.
- Contraindications: Hypersensitivity, recent MI or unstable angina.
- Drug Interactions: CYP3A4 substrates/inhibitors/inducers, MAOIs, stimulants.
- Pregnancy & Breastfeeding: Limited data, potential risks to the fetus/infant.
- Dosage: 150-250 mg/day for adults.
- Monitoring Parameters: Blood pressure, heart rate, skin reactions, psychiatric symptoms.
Popular Combinations
No specific popular drug combinations involving armodafinil are widely recommended or used.
Precautions
- Screen for pre-existing medical conditions, especially cardiovascular and psychiatric disorders.
- Pregnant women: Use only if benefits outweigh risks.
- Breastfeeding mothers: Use with caution and monitor infant closely.
- Children & Elderly: Exercise caution and consider lower doses.
- Lifestyle: Avoid alcohol; driving restrictions may be necessary.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Armodafinil?
A: The standard adult dosage is 150 mg once daily, taken in the morning for narcolepsy and OSA, and 1 hour before work shift for SWSD. It can be increased to 250 mg/day if needed. Lower doses may be necessary for elderly patients and those with hepatic impairment. Pediatric dosing is not well established.
Q2: How does Armodafinil differ from Modafinil?
A: Armodafinil is the R-enantiomer of modafinil. It is considered the more active component of the racemic modafinil and has a slightly longer half-life.
Q3: Can Armodafinil be used in patients with cardiovascular disease?
A: It should be used with caution and increased monitoring in patients with pre-existing cardiovascular disease.
Q4: What are the most serious side effects of Armodafinil?
A: Serious side effects can include severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), angioedema, anaphylaxis, multi-organ hypersensitivity reactions, and psychiatric symptoms (worsening depression, psychosis, mania).
Q5: Does Armodafinil interact with hormonal birth control?
A: Yes, armodafinil can decrease the effectiveness of hormonal contraceptives. Alternative or additional methods of contraception should be used.
Q6: Can patients drink alcohol while taking Armodafinil?
A: Alcohol should be avoided as it can increase the risk of side effects like dizziness.
Q7: Can Armodafinil be used during pregnancy?
A: There are limited data on its use during pregnancy. It may be associated with fetal harm. Use only if clearly needed and the benefits outweigh the potential risks.
A: Primarily metabolized in the liver, partially by the CYP3A4 enzyme system.
Q9: What should patients be advised regarding driving while taking Armodafinil?
A: Patients should avoid driving or operating machinery until they know how armodafinil affects them, as it can cause dizziness and sleepiness in some individuals.
Q10: What if a patient misses a dose of Armodafinil?
A: They should take it as soon as they remember, unless it is close to their next scheduled dose. They should not double up on doses.
